A novel gene therapy resulted in the sustained release of clotting factor VIII (FVIII) over several years in a small cohort of patients with hemophilia A, according to a new study published in the New England Journal of Medicine.

The study was an international multicenter phase 1/2 trial led by the Children’s Hospital of Philadelphia (CHOP) and funded by Spark Therapeutics.

A total of 16 out of 18 patients with hemophilia who received treatment with SPK-8011 maintained expression of FVIII during the study’s observation period (mean, 36.6 months; range, 5.5-50.3 months). Twelve patients were followed for 2 years or more and did not show signs of decreasing FVIII activity.

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The patients had an overall reduction of 91.5% in annualized bleed rates. The patients had a median bleed rate of 8.5 events per year prior to treatment which reduced to a mean of 0.3 per year.

“The results of this study offer compelling data to support the current approach to hemophilia A gene transfer can indeed confer stable factor VIII expression over multiple years for near disease ameliorating effect,” Lindsey A. George, MD, director of Clinical In Vivo Gene Therapy, attending hematologist at Children’s Hospital of Philadelphia, and lead investigator of the study said.

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Two of the enrolled patients lost their FVIII expression within the first year of the study, presumably due to an anti-adeno-associated virus (AAV) capsid immune response that was not sensitive to treatment with immunosuppressants.

“Future research will aim to further improve on this work to safely achieve sustained, stable, and predictable FVIII levels in all hemophilia A patients,” Dr. George said.

A total of 18 patients with hemophilia A enrolled in the study and received 1 of 4 different doses of SPK-8011, ranging from 5 x 1011 vector genomes per kilogram of body weight up to 2 x 1012 vector genomes per kilogram.

SPK-8011 is a novel recombinant AAV designed to cause the expression of FVIII in the patients’ liver cells. Some patients received glucocorticoids to prevent or treat a presumed AAV capsid immune response within the first 52 weeks after administration of the treatment.


Children’s Hospital of Philadelphia. CHOP-led study shows novel gene therapy for hemophilia A leads to sustained expression of clotting factor and reduced bleeding events. News release. Children’s Hospital of Philadelphia; November 17, 2021.

George LA, Monahan PE, Eyster ME, et al. Multiyear factor VIII expression after AAV gene transfer for hemophilia A. N Engl J Med. 2021;385(21):1961-1973. doi:10.1056/NEJMoa2104205